Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: zarhym on December 29, 2017, 12:29:07 AM
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I am trying to synthesis a hydroxymethyl imidazole following a literature procedure.
DOI: 10.1039/A701751K,
J. Chem. Soc., Perkin Trans. 1, 1997,0, 2203-2210.
My understanding of this imidazole formation mechanism is through loss of two water molecules to get a alkene intermediate. This intermediate further hydrolysis under acidic condition to for a hydroxymethyl imidazole.
Am I understand this mechanism correctly?
I tried reaction by mixing trifluoroacetamidine and butane-2,3-dione in water and stirred at R.T. overnight.
I am also trying neat reaction at 60 degree C.
Nothing happened so far.
Is there any suggestions?
Thanks a lot.
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Probably, fluorine atom forms H-bonds with the amidine group and the HCl that inhibit the reaction.
Try to work at temperatures higher than 70-80oC, in order to offer enough heat to break any fluorine H-bond. It might work.
Also, add a little amount of aqueous HCl.
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The CF3 group is strongly electron withdrawing so it reduces the reactivity of the nitrogen atoms, that might be why the reaction is not working for your. Maybe heat it more ? Also, the amine group is protonated which could also have some effect on reactivity, maybe try to add some base like TEA. It could increase the reactivity of the amine via neutralization while still being acidic enough to catalyze the reaction further...
trying more acid as suggested by pgk could work as well
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I guess I am finally getting something after several experiments. I'll update it soooooon.
Thanks for your suggestions.
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This synthesis approach does not work eventually. The reason is strongly electron withdrawing nature of the CF3 group. We tried replacing this CF3 group with a alkyl group, which gives clean reaction with high yield. However, with CF3 group, it never works and only gives messy reaction.